Quinazoline derivatives and process of making same



Patented Nov. 14, 1950 QUINAZOLINE DERIVATIVES AND PROCESS OF MAKING SAME Eduard Moergeli, Neuewelt, Paul 'Sutter, Binningen, and Walter Kern, Sissah, Switzerland, assignors to Ciba Limited, Basel, Switzerland, a Swiss firm No Drawing. Application June 24, 1947, Serial No. 756,808. In Switzerland July 9, 1946 v 9 Claims. (Cl. 260251) It is known that among quinazoline deriva- Especially suitable in this'conn'ection is the use tives there are valuable intermediate products of phosphorus pentachloride. for the manufacture of dyestuffs (see U. S. Pat- The reaction is advantageously conducted in ent No. 2,187,812 and U. S. Patent No. 2,187,813). an inert diluent or solvent, preferably of high I-Ii therto, however, these quinazoline derivatives boiling point, such as dior tri-chlorobenzene have been made by a troublesome-process, which, and especially nitrobenzene. It is of advantage moreover, in some cases necessitates the use of to increase the temperature rapidly and pref- :starting materials difiicult to obtainerably above 100 C. e. g. to a temperature be- According to the present invention quinazotween 100 C. and, 150 C. and allow the more line derivatives are made in a simple manner by volatile products to distil. The reaction may treating an acylaminoanthraquinone-ortho-nibe brought to completion, by further heating, trile with an agent which is capable of replacing for example, at about 180 C or at an even a hydroxyl group by halogen. higher temperature. i I .,The acylaminoanthraquinone ortho-m'triles The reaction may be formulated as follows;

. Y O u 0 u I NH 0 H NH\0H GL \L H \(JEN H used as starting materials are to a very great but we do not wish to be bound by any theory extent known, and. may in part be obtained very concerning the true course of the reaction. easily by reaction of the corresponding vacyl- The productsobtainedare .quinazoline derivaamino-ortho-halogen-anthraquinone with cutives of the general formula prous cyanide by known methods. Thus, for ex- I CO ample, 2-be-nZoylaminoanthraquinone-3-nitrile is easily obtainablefrofii 2-benzoylamino-3-brom- R2 anthraq'uinone, which can be prepared, for exf F ample, by brominating Z-aminoanthraquinone 40 6 4 3N and benzoylating the amino group. Y 5

i -{The acyl residue in the aforesaid starting ma- {Imogen terials may be of aliphatic, heterocyclic or espej ci ally aromaticnnature, for example, a benzoyl residue. As examples of such starting materials in which R1 represents the residuev q 'iginally present in the acyl group and" there may be mentioned l-benzoylamiho-anthraqilfinone- .2 nitrile, '2 -(para nitrobenzoylamino) -anthraquinone 3 nitrile, 2:6-di-(ben- I zoylamino)-anthraquinone 3:7-dinitrile and, especially, the above named Z-benzoylamino-anrepresents & phthaloyl 178316-118 attached at tWO thraquinone-3-nitri1e. of the positions from 5 to 8. These products As agents capable of replacing a hydroxy] are :in part known, and are valuable'intermegroup by halogen there come into consideration diate products for the manufacture of dyestuffs. substances which are known to convert, for ex- New compounds containing the quinazoline ample, an acid into its corresponding acid halide. r i ue a w positions in he m l le can be obtained by the present process by starting from anthraquinones which contain the ortho-acylamino-nitrile grouping at two places.

The following examples illustrate the invention, the parts being by weight:

Example 1 35.2 parts of 3-cyano-2-benzoylamino-anthraquinone (obtained by heating 3-bromo-2-benzoylaminoanthraquinone with cuprous cyanide and. pyridine in benzene at 190 C.) and 23 parts of phosphorus pentachloride are heated in 250 parts of nitrobenzene first for hour at 110-130 C. and then for hour at 180-185" C. After cooling, the whole is filtered with suction, and the filter residue is washed first with nitrobenzene and then with benzene and dried. There is obtained in good yield 2-phenyl-4-chloro-6z7- phthaloyl-quinazoline of the formula II N K it which melts at about 320 C.

Example 2 A mixture of 30 parts of Z-benzoylamino-anthraquinone-3-nitrile, 44.3 parts of phosphorus pentachloride and 410 parts of nitrobenzene are rapidly distilled to drive off 100 parts. The whole is then allowed to boil under reflux for 20 minutes. After cooling, the product formed is separated after a short time by filtration, washed with a small quantity of nitrobenzene and then with benzene, and dried. There is obtained in this manner a good yield of the product described in Example 1. When recrystallized from nitrobenzene it forms almost colorless prisms which melt at about 325 C.

In a similar manner there is obtained from 2:6- di (benzoylamino) anthraquinone- 3:7-dinitrile a dichloro-diquinazoline of the following nitrile the corresponding 2-(para-nitrophenyl)- 4-chloro-6:7-phthaloyl-quinazoline of the formula p v N y What we claim is:

1. Process for the manufacture of a quinazoline derivative which comprises reacting an acylamino-anthraquinone-orthonitrile with phosphorus pentachloride at elevated temperature, and recovering the said quinazoline derivative.

4 2. Process for the manufacture of a quinazoline derivative which comprises reacting a benzoylamino anthraquinone orthonitrile with phosphorus pentachloride at elevated temperature, 5 and recovering the said quinazoline derivative.

. 3. Process for the manufacture of a quinazoline devirative which comprises reacting a 2-acylamino-anthraquinone-3-nitrile with phosphorus pentachloride at elevated temperature, and recovering the said quinazoline derivative.

4. Process for the manufacture of a quinazoline derivative which comprises reacting a 2-benzoylamino-anthraquinone-3-nitrile with phosphorus pentachloride at elevated temperature, and recovering the said quinazoline derivative.

5. Process for the manufacture of a quinazoline derivative which comprises rapidly heating a 2- benzoylamino-anthraquinone-3-nitrile with phosphorus pentachloride in an inert solvent to a temperature above 100C allowing volatile prod- 1 ucts to escape and heating further to terminate the reaction, and recovering the said quinazoline derivative.

6. Process for the manufacture of a quinazoline derivative which comprises rapidly heating 2- benzoylamino-anthraquinone-3-nitrile with phosphorus pentachloride in an inert solvent to a temperature above 100 0., allowing volatile products to escape and heating further to terminate the reaction, and recovering the said quinazoline derivative.

'7. Process for the manufacture of a quinazoline derivative which comprises rapidly heating Z-(pnitrobenzoyl) amino anthraquinone 3 nitrile r with phosphorus pentachloride in an inert solvent to a temperature above 100 0., allowing volatile products to escape and heating further to terminate the reaction, and recovering the said quinazoline derivative.

8. Process for the manufacture of a quinazoline derivative which comprises rapidly heating 2:6- di- (benzoylamino) anthraquinone-3 7-dinitrile with phosphorus pentachloride in an inert solvent to a temperature above 100 0., allowing volatile products to escape and heating further to terminate the reaction, and recovering the said quinazoline derivative.

9. As a new product the diquinazoline derivative of the formula 3 A f \\1T/ I r EDUARD MOERGELI. PAUL SUTTER. WALTER KERN.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES 'PA Enrs Number Name Date; 2,187,813 Baumann et al 'Jan. 23, 1940 205-206 (1928 edition) 

1. PROCESS FOR THE MANUFACTURE OF A QUINAZOLINE DERIVATIVE WHICH COMPRISES REACTING AN ACYLAMINO-ANTHRAQUINONE-ORTHONITRILE WITH PHOSPHORUS PENTACHLORIDE AT ELEVATED TEMPERATURE, AND RECOVERING THE SAID QUINAZOLINE DERIVATIVE.
 9. AS A NEW PRODUCT THE DIQUINAZOLINE DERIVATIVE OF THE FORMULA 